We are requesting funds for the acquisition of a Zeiss LSM 510 META confocal microscope. Acquisition of the requested state-of-the-art instrument would allow users of this proposal to perform live cell and tissue imaging analyses. The proposed laser scanning confocal microscope will be a major upgrade to our existing light microscope facility on the Science Hill campus of Yale University. Principal users designated in this proposal are already using optical imaging techniques to answer a variety of basic, fundamental questions in biology. The requested instrument will enhance their ability to perform complex and cutting edge image analysis required by many of the modern model organisms like zebrafish, Drosophila, plants and mice. Research activities facilitated by this instrument will include investigation of innate immunity (Dinesh-Kumar, Principal Investigator), cytoskeleton and molecular motors (Mark Mooseker, co-investigator), Drosophila olfactory system (John Carlson), light regulated developmental switch (Xing-Wang Deng), origin and induction of neural crest stem cells (Martin Garcia-Castro), ubiquitin/proteasome-mediated targeted proteolysis (Mark Hochstrasser), zebrafish somitogenesis (Scott Holley), cellular and molecular mechanisms of synaptogenesis (Haig Keshishian), cytoskeletal dynamics and cellular motility (Thomas Pollard), chemical biology of protein-protein and protein-DNA interactions inside the cell (Alanna Schepartz), axonal, dendritic and spinal abnormalities leading to neuronal developmental defects and cognitive impairment (Elke Stein), learning and memory (David Wells), and asymmetric cell division in neurogenesis and stem-cell maintenance (Weimin Zhong). The requested state-of-the-art instrument undoubtedly will have a significant impact on the research programs on the Science Hill side of the Yale campus by filling a substantial void in our available instrumentation. Given the current and future centrality of fluorescence microscopy in studying the dynamics and complexity of biological processes, access to state-of-the-art instrument will maximize the impact of our currently funded NIH research. [unreadable] [unreadable] [unreadable]